Norepinephrine is a sympathomimetic amine which functions as a peripheral vasoconstrictor (alpha-adrenergic action) and as an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action). It is also known as l-arterenol, levarterenol or l-norepinephrine or noradrenaline.
Norepinephrine Bitartrate, a catecholamine is chemically (-)-α-(aminomethyl)-3,4-dihydroxybenzyl alcohol tartrate (1:1) (salt) monohydrate and has the following structural formula:

Norepinephrine (NE) is administered by intravenous infusion for blood pressure control in certain acute hypotensive states (e.g., pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesthesia, myocardial infarction, septicemia, blood transfusion, and drug reactions) and as an adjunct in the treatment of cardiac arrest and profound hypotension.
The commercial available injectable products of nor-epinephrine solutions for example, nor-epinephrine pre-concentrate solution marketed in the United States under the brand name LEVOPHED® and the solution of nor-epinephrine marketed by Cardinal Health Ltd., UK, use sodium bisulfite or sodium metabisulfite as antioxidants. A clear warning with respect to allergic reactions is included in the labels of these products, which entails cautious use of these products by the patients. The use of sulphites or sulphur is reported to cause allergic-type reactions such as anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible persons. Indeed, the symptoms of an allergic reaction to sulfites may exacerbate the condition being treated. This exacerbation is especially critical given that nor-epinephrine is often used in emergency situations where further compromising a patient with an allergic reaction is disadvantageous.
Nor-epinephrine is known to be susceptible to oxidation and degradation in presence of oxygen, particularly when present in aqueous solutions. The degradation is undesirable as it results in loss of titer of the active ingredient, formation of compounds which have undesirable physiological effects, and the appearance of a dark colour, which makes the solution offensive and unmarketable. Moreover, nor-epinephrine is known to exist in two different stereoisomeric forms: R (−) isomer and S (+) isomer, the R(−) isomer is reported to have better affinity at various receptors and thus, more potent than the S(+) isomer. The S-isomer has minimal to almost negligible activity.
The present inventors have discovered a parenteral dosage form wherein the aqueous solution of nor-epinephrine is free of sulphite antioxidant and is ready to administer. The ready-to-administer aqueous solution in the containers is not only stable at room temperature for prolonged periods of time, but also shows minimal conversion to less active S-isomer during the shelf life of the product. Further, the parenteral dosage form avoids the reconstitution or dilution step prior to intravenous infusion, thus eliminating the risk of any potential calculation or dilution error as well as risk of microbiological contamination during handling.